The overall objective of this project is to find some useful alternatives to the presently available methods of oligonucleotide synthesis. Subsequently, the best new method would be applied to some current problems of molecular biology, for example, the synthesis of a gene or important RNA fragments. The more specific aims are as follows: 1. The elaboration of the best method for the chemical synthesis of the 5'-deoxy-5'thio analogs of DNA and RNA in stepwise fashion; the synthesis of polymers of alternating sequences. 2. Determination of template activity of the above thio analogs with respect to the action of DNA polymerase, RNA polymerase, and in protein synthesis. 3. Work towards the synthesis of a gene analog and a tRNA analog. 4. Replication of selected templates by a purely chemical process. 5. A study of poly functional systems capable of achieving specific 3'-5' esterification.